Thyroid hormone blood transport

As discussed in the previous section, steroid and thyroid hormones are transported in the blood bound to plasma proteins. The serum concentrations of free hormone (H), plasma protein (P), and bound hormone (HP) are in equilibrium ... 

Amine hormones include the thyroid hormones and the catecholamines. The thyroid hormones tend to be biologically similar to the steroid hormones. They are mainly insoluble in the blood and are transported predominantly (>99%) bound to proteins. As such, these hormones have longer half-lives (triiodothyronine, t3, = 24 h thyroxine, T4, = 7 days). Furthermore, thyroid hormones cross cell membranes to bind with intracellular receptors and may be administered orally (e.g., synthryoid). In contrast to steroid hormones, however, thyroid hormones have the unique property of being stored extra-cellularly in the thyroid gland as part of the thyroglobulin molecule. 

Steroid and thyroid hormones are minimally soluble in the blood. Binding to plasma proteins renders them water soluble and facilitates their transport. Protein binding also prolongs the circulating half-life of these hormones. Because they are lipid soluble, they cross cell membranes easily. As the blood flows through the kidney, these hormones would enter cells or be... 

Transport. A wellknown transport protein is hemoglobin in the erythrocytes (bottom left). It is responsible for the transport of oxygen and carbon dioxide between the lungs and tissues (see p.282). The blood plasma also contains many other proteins with transport functions. Prealbumin (transthyretin middle), for example, transports the thyroid hormones thyroxin and triiodothyronine. Ion channels and other integral membrane proteins (see p.220) facilitate the transport of ions and metabolites across biological membranes. 

W. M. Partridge, Carrier mediated transport of thyroid hormones through the rat blood brain barrier. Primary role of albumin bound hormone, J. Clin. Invest. 64 145-154 (1979). 

In this chapter we will first briefly describe the major parameters controlling the level of thyroid hormone production and its concentration by the target cell (see Ref. 6), i.e., biosynthesis and output from the thyroid gland, transport in the blood, conversion of the prohormone thyroxine (T4), to the active form, 3,5,3 -triiodo-... 

The concentration of thyroid hormones in a given responsive cell depends on a number of factors (Fig. 2) including 1) the production of the two major hormones in the thyroid gland and their secretion in the blood (see Ref. 6) (both the synthesis and the secretion processess are themselves regulated by TSH) 2) the transport of T4 and T3 in the blood and then their degradation in the liver and in the kidney 3) the uptake of thyroid hormones by the different target cells 4) the peripheral conversion of the prohormone, T4, to the active (T3) and the inactive ( reverse T3 or r-T3) derivatives in the responsive cells. 

Membrane-containing fractions displaying T3-binding activities have been detected in a variety of cell types [13-16], Rat liver [15] and erythrocyte [16] plasma membranes, for instance, contain T4- and T3-binding sites with affinities ranging from 1 to 10 x 10 10 M for T3. It is not clear whether the function of these sites is related to the transport of thyroid hormones from the blood to the cell or if they represent receptors responsible for non-nuclear effects of thyroid hormones [17,18]. 

The thyroidogenic effects and corresponding biochemical mechanisms of PCBs and other OHS were recently reviewed by Brouwer et al. [44]. The selective retention of certain OH-PCB congeners in blood (Sect. 5.2.2 and 5.3.2) is concomitant with effects observed on the plasma levels of thyroid hormones. Thyroxine is transported in plasma by a protein complex consisting of TTR and retinol binding protein (RBP). Rats administered CB-77 were shown to have reduced plasma levels of both thyroxine and retinol [196]. A major metabolite of CB-77, 4-OH-3,3, 4, 5-tetrachlorobiphenyl, was identified as the active compound [40]. The same hydroxy-PCB metabolite was found to be retained in mouse fetal soft tissue [191,197]. 

Thyroid hormones are present in the blood in two forms protein-bound and free hormone. Although the fiw portion constitutes only approximately 1% of the total hormone, it is the metaboli-cally active form and the one that is transported into cells to exert its effects. Many drugs have been... 

Thiamine absorption occurs primarily in the proximal small intestine by both a saturable (thiamine transporter) process at low concentration (Ipmol/L, or lower) and by simple passive diffusion beyond that, though percentage absorption diminishes with increased dose. The absorbed thiamine undergoes intracellular phosphorylation, mainly to the pyrophosphate, but at the serosal side 90% of the transferred thiamine is in the firee form. Thiamine uptake is enhanced by thiamine deficiency and reduced by thyroid hormone, diabetes, and ethanol ingestion. The gene for the specific thiamine transporter has been identified, and the transporter cloned. Thiamine is carried by the portal blood to the liver. The firee vitamin occurs in the plasma, but the coenzyme, TPP, is the primary cellular component. Approximately 30 mg is stored in the body with 80% as the pyrophosphate, 10% as triphosphate, and the rest as thiamine and its monophosphate. About half of the body stores are found in skeletal muscles, with much of the remainder in heart, liver, kidneys, and nervous tissues (including the brain, which contains most of the triphosphate). 

For example, alternative transcription-control elements regulate expression of the mammalian gene that encodes transthyretin (TTR), which transports thyroid hormone in blood and the cerebrospinal fluid that surrounds the brain... 

TRANSPORT OF THYROID HORMONES IN THE BLOOD Iodine circulates as both organic iodine (95%) and inorganic iodide (5%). Most organic iodine is in T (90-95%), while Tj contains approximately 5%. Both T and T are transported in the blood in strong but noncovalent association with plasma proteins. 

Endocrine hormones are defined as compounds, secreted from specific endocrine cells in endocrine glands, that reach their target cells by transport through the blood. Insulin, for example, is an endocrine hormone secreted from the p cells of the pancreas. Classic hormones are generally divided into the structural categories of polypeptide hormones (e.g., insulin -see Chapter 6, Fig. 6.15 for the structnre of insnlin ), catecholamines such as epinephrine (which is also a nen-rotransmitter), steroid hormones (which are derived from cholesterol), and thyroid hormone (which is derived from tyrosine). Many of these endocrine hormones also exert paracrine or autocrine actions. The hormones that regnlate metabolism are discussed throughout this chapter and in snbseqnent chapters of this text. 

Lipophilic hormones that use intracellular gene-specific transcription factors include the steroid hormones, thyroid hormone, retinoic acid (active form of vitamin A), and vitamin D (Fig. 11.8). Because these compounds are water-insoluble, they are transported in the blood bound to serum albumin, which has a hydrophobic binding pocket, or to a more specific transport protein, such as steroid hormonebinding globulin (SHBG) and thyroid hormone-binding globulin (TBG). The intracellular receptors for these hormones are structurally similar and are referred to as the steroid hormone/thyroid hormone superfamily of receptors. 

---